MX2015001793A - Derivados de benceno sustituidos con arilo y heteroarilo como moduladores de las trayectorias de señalizacion de cinasa pi3. - Google Patents
Derivados de benceno sustituidos con arilo y heteroarilo como moduladores de las trayectorias de señalizacion de cinasa pi3.Info
- Publication number
- MX2015001793A MX2015001793A MX2015001793A MX2015001793A MX2015001793A MX 2015001793 A MX2015001793 A MX 2015001793A MX 2015001793 A MX2015001793 A MX 2015001793A MX 2015001793 A MX2015001793 A MX 2015001793A MX 2015001793 A MX2015001793 A MX 2015001793A
- Authority
- MX
- Mexico
- Prior art keywords
- phenyl
- substituted
- alkyl
- sulfonyl
- thiadiazol
- Prior art date
Links
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title abstract description 11
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 title description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 title description 2
- 230000019491 signal transduction Effects 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 61
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 37
- 201000010099 disease Diseases 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 22
- 230000004900 autophagic degradation Effects 0.000 claims abstract description 21
- 230000037361 pathway Effects 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 240
- -1 -NRmRn Chemical group 0.000 claims description 148
- 125000000217 alkyl group Chemical group 0.000 claims description 118
- 229910052739 hydrogen Inorganic materials 0.000 claims description 59
- 239000001257 hydrogen Substances 0.000 claims description 56
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 52
- 125000003545 alkoxy group Chemical group 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
- 150000002367 halogens Chemical group 0.000 claims description 42
- 125000002947 alkylene group Chemical group 0.000 claims description 41
- 238000011282 treatment Methods 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 19
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 206010012289 Dementia Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 201000002832 Lewy body dementia Diseases 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 230000032683 aging Effects 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 208000019622 heart disease Diseases 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 230000009885 systemic effect Effects 0.000 claims description 3
- METQSAABMLHWQI-UHFFFAOYSA-N (4-chlorophenyl)-[4-(1,3,4-thiadiazol-2-ylamino)phenyl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)C(C=C1)=CC=C1NC1=NN=CS1 METQSAABMLHWQI-UHFFFAOYSA-N 0.000 claims description 2
- POVLEEZLVJLEBQ-UHFFFAOYSA-N 2-[5-[[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]amino]-1,3,4-thiadiazol-2-yl]ethanol Chemical compound S1C(CCO)=NN=C1NC1=CN=C(S(=O)(=O)C=2C=CC(Cl)=CC=2)C=N1 POVLEEZLVJLEBQ-UHFFFAOYSA-N 0.000 claims description 2
- 206010003694 Atrophy Diseases 0.000 claims description 2
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 2
- HKUJIISFLUFFCV-UHFFFAOYSA-N [4-chloro-3-(trifluoromethyl)phenyl]-[4-(1,3,4-thiadiazol-2-ylamino)phenyl]methanone Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(C(=O)C=2C=CC(NC=3SC=NN=3)=CC=2)=C1 HKUJIISFLUFFCV-UHFFFAOYSA-N 0.000 claims description 2
- 230000037444 atrophy Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- WMIYGLJKCSOJFI-UHFFFAOYSA-N 1-n-[4-chloro-3-(trifluoromethyl)phenyl]-4-n-(1,3,4-thiadiazol-2-yl)benzene-1,4-diamine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(NC=2C=CC(NC=3SC=NN=3)=CC=2)=C1 WMIYGLJKCSOJFI-UHFFFAOYSA-N 0.000 claims 1
- YHWARMRGGTVWMO-UHFFFAOYSA-N 5-(aziridin-1-ylmethyl)-n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC(S1)=NN=C1CN1CC1 YHWARMRGGTVWMO-UHFFFAOYSA-N 0.000 claims 1
- 208000034189 Sclerosis Diseases 0.000 claims 1
- GUNNOKLWFBJUQO-UHFFFAOYSA-N n-[2-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylpyrimidin-5-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=CC(NC=3SC=NN=3)=CN=2)=C1 GUNNOKLWFBJUQO-UHFFFAOYSA-N 0.000 claims 1
- YUVKNKMPXOKAQO-UHFFFAOYSA-N n-[2-chloro-4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)C=2C=C(Cl)C(NC=3SC=NN=3)=CC=2)=C1 YUVKNKMPXOKAQO-UHFFFAOYSA-N 0.000 claims 1
- KXSGSZSNBGOCDY-UHFFFAOYSA-N n-[3-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl-1,2,4-triazin-6-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=NC(NC=3SC=NN=3)=CN=2)=C1 KXSGSZSNBGOCDY-UHFFFAOYSA-N 0.000 claims 1
- TXNOSKGLWXEJOQ-UHFFFAOYSA-N n-[4-(2-chloro-4-fluorophenyl)sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound ClC1=CC(F)=CC=C1S(=O)(=O)C(C=C1)=CC=C1NC1=NN=CS1 TXNOSKGLWXEJOQ-UHFFFAOYSA-N 0.000 claims 1
- JJBRYZUGWJJTPU-UHFFFAOYSA-N n-[4-(4-fluorophenyl)sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(F)=CC=C1S(=O)(=O)C(C=C1)=CC=C1NC1=NN=CS1 JJBRYZUGWJJTPU-UHFFFAOYSA-N 0.000 claims 1
- SZGLXKSNLYOORR-UHFFFAOYSA-N n-[4-[3-(trifluoromethoxy)phenyl]sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound FC(F)(F)OC1=CC=CC(S(=O)(=O)C=2C=CC(NC=3SC=NN=3)=CC=2)=C1 SZGLXKSNLYOORR-UHFFFAOYSA-N 0.000 claims 1
- KAQZQFPYKRJGSK-UHFFFAOYSA-N n-[4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)C=2C=CC(NC=3SC=NN=3)=CC=2)=C1 KAQZQFPYKRJGSK-UHFFFAOYSA-N 0.000 claims 1
- PHYYVLXFAQCOLF-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl-3-fluorophenyl]-1,3,4-thiadiazol-2-amine Chemical compound C=1C=C(S(=O)(=O)C=2C=C(C(Cl)=CC=2)C(F)(F)F)C(F)=CC=1NC1=NN=CS1 PHYYVLXFAQCOLF-UHFFFAOYSA-N 0.000 claims 1
- YVUIQHKJPBSQSU-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1,3,4-oxadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3OC=NN=3)=CC=2)=C1 YVUIQHKJPBSQSU-UHFFFAOYSA-N 0.000 claims 1
- SZOPGUATBWMHNR-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1h-1,2,4-triazol-5-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3NN=CN=3)=CC=2)=C1 SZOPGUATBWMHNR-UHFFFAOYSA-N 0.000 claims 1
- FFPBFHRJGZTMQU-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1h-imidazol-5-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3NC=NC=3)=CC=2)=C1 FFPBFHRJGZTMQU-UHFFFAOYSA-N 0.000 claims 1
- AXWHUZXBRSKCLL-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1h-pyrrol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3NC=CC=3)=CC=2)=C1 AXWHUZXBRSKCLL-UHFFFAOYSA-N 0.000 claims 1
- URTSUAFRXCZONN-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-2h-tetrazol-5-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC3=NNN=N3)=CC=2)=C1 URTSUAFRXCZONN-UHFFFAOYSA-N 0.000 claims 1
- SKFKQHGEQGJBPF-UHFFFAOYSA-N n-[4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]phenyl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(CC=2C=CC(NC=3SC=NN=3)=CC=2)=C1 SKFKQHGEQGJBPF-UHFFFAOYSA-N 0.000 claims 1
- JGXKXZOVOZYZTI-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC1=NN=CS1 JGXKXZOVOZYZTI-UHFFFAOYSA-N 0.000 claims 1
- IQIARBSSAQBFHI-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-5-(morpholin-4-ylmethyl)-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC(S1)=NN=C1CN1CCOCC1 IQIARBSSAQBFHI-UHFFFAOYSA-N 0.000 claims 1
- HXQHDPILLFXWCT-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-5-(piperidin-1-ylmethyl)-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC(S1)=NN=C1CN1CCCCC1 HXQHDPILLFXWCT-UHFFFAOYSA-N 0.000 claims 1
- CXKMZZFUCHIDLF-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-5-[(4-methylpiperazin-1-yl)methyl]-1,3,4-thiadiazol-2-amine Chemical compound C1CN(C)CCN1CC(S1)=NN=C1NC1=CN=C(S(=O)(=O)C=2C=CC(Cl)=CC=2)C=N1 CXKMZZFUCHIDLF-UHFFFAOYSA-N 0.000 claims 1
- SCKSIULALHNVKP-UHFFFAOYSA-N n-[5-(4-fluorophenyl)sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(F)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC1=NN=CS1 SCKSIULALHNVKP-UHFFFAOYSA-N 0.000 claims 1
- KYUNDAOKBURETM-UHFFFAOYSA-N n-[5-[4-(trifluoromethoxy)phenyl]sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC1=NN=CS1 KYUNDAOKBURETM-UHFFFAOYSA-N 0.000 claims 1
- CYNPWXCNCPZFOB-UHFFFAOYSA-N n-[5-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=CC(NC=3SC=NN=3)=NC=2)=C1 CYNPWXCNCPZFOB-UHFFFAOYSA-N 0.000 claims 1
- SDMIDNGLYTZDHC-UHFFFAOYSA-N n-[6-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl-1,2,4,5-tetrazin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=NC(NC=3SC=NN=3)=NN=2)=C1 SDMIDNGLYTZDHC-UHFFFAOYSA-N 0.000 claims 1
- QMXJMPRWYDCXCG-UHFFFAOYSA-N n-[6-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylpyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=CC(NC=3SC=NN=3)=CC=2)=C1 QMXJMPRWYDCXCG-UHFFFAOYSA-N 0.000 claims 1
- PUCFTQBPVTZKNA-UHFFFAOYSA-N n-[[5-[[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]amino]-1,3,4-thiadiazol-2-yl]methyl]methanesulfonamide Chemical compound S1C(CNS(=O)(=O)C)=NN=C1NC1=CN=C(S(=O)(=O)C=2C=CC(Cl)=CC=2)C=N1 PUCFTQBPVTZKNA-UHFFFAOYSA-N 0.000 claims 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 113
- 238000006243 chemical reaction Methods 0.000 description 106
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
- 239000000203 mixture Substances 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- 125000003118 aryl group Chemical group 0.000 description 40
- 125000001072 heteroaryl group Chemical group 0.000 description 40
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- 125000000623 heterocyclic group Chemical group 0.000 description 36
- 125000000392 cycloalkenyl group Chemical group 0.000 description 29
- 229910001868 water Inorganic materials 0.000 description 26
- 239000003208 petroleum Substances 0.000 description 25
- 239000007787 solid Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 23
- 125000000547 substituted alkyl group Chemical group 0.000 description 20
- 238000004809 thin layer chromatography Methods 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- 235000019441 ethanol Nutrition 0.000 description 17
- 238000012544 monitoring process Methods 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- 125000003107 substituted aryl group Chemical group 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 125000000304 alkynyl group Chemical group 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
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- 208000024891 symptom Diseases 0.000 description 16
- 125000005843 halogen group Chemical group 0.000 description 15
- 125000005842 heteroatom Chemical group 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 125000003342 alkenyl group Chemical group 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 230000008569 process Effects 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 12
- 229940002612 prodrug Drugs 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 125000005017 substituted alkenyl group Chemical group 0.000 description 12
- 125000004426 substituted alkynyl group Chemical group 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
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- 125000004429 atom Chemical group 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 9
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 9
- 125000003277 amino group Chemical group 0.000 description 9
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- 238000005516 engineering process Methods 0.000 description 9
- 150000002500 ions Chemical class 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 125000005283 haloketone group Chemical group 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea group Chemical group NC(=S)N UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 8
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 7
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 125000001153 fluoro group Chemical group F* 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
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Classifications
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
- C07D257/06—Five-membered rings with nitrogen atoms directly attached to the ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US201261681585P | 2012-08-09 | 2012-08-09 | |
| PCT/US2013/054200 WO2014026039A2 (en) | 2012-08-09 | 2013-08-08 | Aryl-and heteroaryl-substituted benzene derivatives as modulators of pi3-kinase signalling pathways |
Publications (1)
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| MX2015001793A true MX2015001793A (es) | 2015-05-07 |
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| US (1) | US20150197513A1 (enExample) |
| EP (1) | EP2882726A4 (enExample) |
| JP (1) | JP2015524483A (enExample) |
| CN (1) | CN104703985A (enExample) |
| CA (1) | CA2881472A1 (enExample) |
| HK (1) | HK1206331A1 (enExample) |
| MX (1) | MX2015001793A (enExample) |
| WO (1) | WO2014026039A2 (enExample) |
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| BR112017003745A2 (pt) | 2014-08-29 | 2017-12-05 | Tes Pharma S R L | inibidores de semialdeído descarboxilase de ácido alfa-amino-beta-carboximucônico |
| WO2016113205A1 (de) | 2015-01-13 | 2016-07-21 | Bayer Pharma Aktiengesellschaft | Substituierte pentafluorethylpyrimidinone und ihre verwendung |
| CN108947985A (zh) * | 2017-05-22 | 2018-12-07 | 苏州偶领生物医药有限公司 | 用作自噬调节剂的化合物及其制备方法和用途 |
| CN111094278B (zh) * | 2017-09-13 | 2023-07-14 | 诺华股份有限公司 | 二苯基衍生物及其用途 |
| CN111372579B (zh) * | 2017-10-30 | 2023-08-22 | 神经孔疗法股份有限公司 | 取代的苯基磺酰基苯基三唑硫酮和其用途 |
| IL277071B2 (en) | 2018-03-08 | 2024-07-01 | Incyte Corp | AMINOPYRAZINE DIOL COMPOUNDS AS PI3K-y INHIBITORS |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| JP7506903B2 (ja) * | 2019-11-01 | 2024-06-27 | 日本メナード化粧品株式会社 | Il-37産生促進剤 |
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| GB1476503A (en) * | 1973-06-21 | 1977-06-16 | Sterling Drug Inc | 1-arylamino-and 1-arylimino-pyrroles and preparation thereof |
| DE3307506A1 (de) * | 1983-03-03 | 1984-09-06 | Agfa-Gevaert Ag, 5090 Leverkusen | Fotografisches aufzeichnungsmaterial mit inhibitorvorlaeuferverbindungen |
| US20020183306A1 (en) * | 2001-05-30 | 2002-12-05 | Pfizer Inc. | Combination treatment for sleep disorders including sleep apnea |
| US20040235877A1 (en) * | 2001-09-14 | 2004-11-25 | Natsuki Ishizuka | Novel use of tricyclic compound |
| US20050228031A1 (en) * | 2004-04-13 | 2005-10-13 | Bilodeau Mark T | Tyrosine kinase inhibitors |
| US7429667B2 (en) * | 2005-01-20 | 2008-09-30 | Ardea Biosciences, Inc. | Phenylamino isothiazole carboxamidines as MEK inhibitors |
| BRPI0608910A2 (pt) * | 2005-05-09 | 2010-02-17 | Achillion Pharmaceuticals Inc | uso de um composto da fórmula ou um sal ou hidrato farmaceuticamente aceitável desse, composto ou sal ou hidrato do mesmo, composição farmacêutica e composição farmacêutica embalada |
| JP2009500351A (ja) * | 2005-07-04 | 2009-01-08 | ドクター レディズ ラボラトリーズ リミテッド | Ampkアクチベータとしてのチアゾール誘導体 |
| WO2009117444A1 (en) * | 2008-03-17 | 2009-09-24 | Northeastern University | Inhibitors of fatty acid amide hydrolase and monoacylglycerol lipase for modulation of cannabinoid receptors |
| UY32582A (es) * | 2009-04-28 | 2010-11-30 | Amgen Inc | Inhibidores de fosfoinositida 3 cinasa y/u objetivo mamífero |
| EP2462128B1 (en) * | 2009-08-04 | 2016-09-21 | Amira Pharmaceuticals, Inc. | Compounds as lysophosphatidic acid receptor antagonists |
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2013
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- 2013-08-08 WO PCT/US2013/054200 patent/WO2014026039A2/en not_active Ceased
- 2013-08-08 MX MX2015001793A patent/MX2015001793A/es unknown
- 2013-08-08 EP EP13828347.8A patent/EP2882726A4/en not_active Withdrawn
- 2013-08-08 CN CN201380052581.7A patent/CN104703985A/zh active Pending
- 2013-08-08 CA CA2881472A patent/CA2881472A1/en not_active Abandoned
- 2013-08-08 JP JP2015526717A patent/JP2015524483A/ja not_active Abandoned
- 2013-08-08 HK HK15106801.9A patent/HK1206331A1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20150197513A1 (en) | 2015-07-16 |
| CN104703985A (zh) | 2015-06-10 |
| JP2015524483A (ja) | 2015-08-24 |
| WO2014026039A2 (en) | 2014-02-13 |
| CA2881472A1 (en) | 2014-02-13 |
| EP2882726A4 (en) | 2016-04-06 |
| HK1206331A1 (en) | 2016-01-08 |
| EP2882726A2 (en) | 2015-06-17 |
| WO2014026039A4 (en) | 2014-08-14 |
| WO2014026039A3 (en) | 2014-06-26 |
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